# Striatum Wide Dynamics and Neuromodulation of Cell-Type Specific Striatum Populations during Learning

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $575,197

## Abstract

PROJECT SUMMARY/ABSTRACT
The striatum, the principle input nucleus of the basal ganglia, is a central mediator of associative learning for
evaluating, motivating, and directing appropriate actions in response to external stimuli. Behavioral studies
have suggested that distinct sub-regions of the striatum make unique contributions to adaptive learning, and
that dysfunction in particular corticostriatal circuits may explain the range of learning and motivational deficits
observed in basal ganglia disorders such as Parkinson’s Disease and addiction. Learning related changes in
striatum neurons are widely believed to be driven by dopamine dependent bi-directional synaptic plasticity in
distinct populations of direct and indirect pathway output neurons. This proposal will investigate how large
scale, cell-type specific neural dynamics across distinct sub-networks of the striatum evolve to evaluate
external cues, select appropriate actions, and invigorate movement over the course of sensori-motor learning.
We will use a new optical approach we have developed to monitor and manipulate signals from two distinct
output pathways of the striatum across a large 3-dimensional volume in head-fixed behaving mice during types
of learning known to depend on different striatal sub-circuits. We will investigate the causal contribution of
distributed dopaminergic signaling to bi-directional learning related changes in striatum output neurons by
measuring and manipulating patterns of region specific dopamine release across the striatum volume during
learning. Finally, we will employ 2-photon calcium imaging to track activity in hundreds of individual striatum
neurons across days and determine how large scale learning related changes in striatum ensembles result
from day to day changes at the single cell and network levels. Results from the proposed studies will provide
new insight into how spatiotemporal changes in cell-type specific striatum output mediate central aspects of
adaptive learning and action selection, and ultimately, how neurological disorders of learning and motivation
might result from regional dysfunctions in distinct striatum networks.

## Key facts

- **NIH application ID:** 10398129
- **Project number:** 5R01MH125835-02
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Mark W Howe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $575,197
- **Award type:** 5
- **Project period:** 2021-04-27 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398129

## Citation

> US National Institutes of Health, RePORTER application 10398129, Striatum Wide Dynamics and Neuromodulation of Cell-Type Specific Striatum Populations during Learning (5R01MH125835-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10398129. Licensed CC0.

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